Suppressor T-cells play an important role in the biology of human tumors. The focus of the work we propose is the suppressor T-cell subset which is characterized by the possession of a surface receptor for histamine of the H2 type (H2Rplus). Previously we have studied this cell from biochemical and immunological perspectives. This has included the solubilization, characterization and purification of specific H1 an H2 receptors from its surface. In addition, we have demonstrated that the immature percursor of this cell requires thymic stimulation to express the H2 receptor, and have partially purified a factor from calf thymus which specifically induces the H2 receptor. Furthermore, we have shown that this cell can be activated by histamine to become a functional suppressor cell. This effect of histamine is mediated through the H2 site as evidenced by the ability of cimetidine (an H2 antagonist) to block it. We now propose a detailed study of the relationship of this specific suppressor cell to malignant disease. In order to do so we will characterize and quantitate histamine receptors on the T-cells of patients and animals with malignant tumors; determine the effect of histamine and its antagonists/agonists on the functional immunological activity of the H2Rplus cell including lymphocyte-mediated tumor cytotoxicity and suppression; determine if histamine and its antagonists/agonists have a role in the therapy of cancer based on studies of their effect on suppressor cells in an animal model; and, determine the role that serum histamine may have in the pathophysiology of malignancies. We also will study the plasma and serum of patients with malignancies for the presence of a circulating factor, analogous to that which we have isolated from calf thymus, which induces histamine H2 receptors on precursor T-cells.